How cancer vaccines work

What Is a Vaccine?

A vaccine fights infection by enabling the body’s natural immune system
to better recognize the pathogen. Immune cells called T cells and B cells
look for specific antigens, usually small pieces of cells or viruses that
the immune system recognizes as foreign, and then reproduce themselves to
better fight the antigens they have found. T cells identify and kill cells
or viruses that contain the antigen, and B cells produce antibodies that
attach to the antigen and kill the cell or virus by indirect means. Each
T and B cell recognizes a different antigen, and when it finds its target,
it makes many copies of itself. This way, the body targets the invasion
by reproducing the cells that go after the specific substance that has already
been identified as foreign. A vaccine just gives the immune system a head
start in this very same process. A vaccine for smallpox contains smallpox
viruses that are somehow disabled so that they cannot infect the vaccine
recipient. When the viral particles enter the cell, the T cells and B cells
that recognize the virus replicate themselves, so the immune system already
has plenty of cells looking for smallpox viruses when the real viruses actually
arrive. The viruses are then attacked immediately upon entrance into the
body and never get the chance to start an infection. The vaccine triggers
the natural immune response so that it is underway before the pathogen even
enters the body.

Cancer vaccines also stimulate an immune response, but direct it towards
cancer cells or viruses that cause cancer. An effective cancer vaccine elicits
both humoral (antibody) responses and cellular (antigen-specific T-cell)
responses. For cancer caused by viruses, the vaccine mechanism is no different
from any other disease; the vaccine simply consists of disabled viruses
that cause cancer, such as human papilloma virus, instead of disabled smallpox
viruses. The FDA has already approved a vaccine against two strains of HPV
that cause nearly 70 percent of all cervical cancers.

Most tumors, however, are not caused by viruses, so the vaccination strategy
must be broadened to deal with a wider variety of cancers. Tumor cells are
human cells that have undergone mutations that cause them to grow and divide
at uncontrolled rates. Because of their mutations, the surfaces of the tumor
cells are slightly different from the surfaces of the normal cells, so the
parts of the surface that are different can be used as antigens to activate
the immune system. However, because they are human cells, the surfaces of
tumor cells are less likely to be recognized as foreign by the immune system.
To complicate matters further, cancer cells sometimes shed molecules that
inhibit immune responses, so considerably more creativity is required to
trigger an immune response against them.

Researchers have developed a variety of strategies to address these issues.
The first step is to identify the molecules that are unique or almost unique
to cancer cells and direct the immune system against them by using them
as vaccines. This will allow the T cells to attack the cancer cells and
the B cells to make antibodies that inhibit the growth of the cells.

In order to strengthen the immune response to the vaccine the antigen
can be modified to make it look more foreign by exaggerating the differences
between it and the corresponding molecule in a normal cell. As long as the
antigen still resembles the tumor antigen enough, the T and B cells that
recognize it will also recognize the tumor cells. The gene that produces
the antigen may also be put into a harmless virus, which inserts the gene
into the DNA of either cancer or normal cells. Once the extra gene is inserted,
these cells will produce far more of the antigen, and therefore cause a
stronger immune response. Either the virus with the gene for the antigen
inserted or a cell that was infected with the virus and is producing many
copies of the antigen may be used as vaccines.

A second strategy involves taking advantage of another type of cell called
an antigen presenting cell (APC), which continually eats various pieces
of matter and displays parts of them on its surface. The T cells and B cells
become activated when they come across an APC with the antigen they recognize
on its surface. Injecting an APC that is displays tumor antigens can be
very useful in stimulating an immune response, as it will activate the correct
T and B cells. In order to get the APC to present tumor antigens, the APC’s
may be infected with a virus that inserts the gene that codes for the tumor
antigen into the DNA of the APC, or the APC’s may be fed tumor antigens
or the DNA or RNA that codes for the antigen.

Antibodies that have binding sites that look like the tumor antigen, called
anti-idiotype antibodies, can also be used to stimulate B cells to make
antibodies against them. Because the B cell makes antibodies against the
part of the anti-idiotype antibody that looks like the tumor antigen, the
B cell’s antibodies also function to disable the tumor cells.

The tumor antigens used to make the vaccines can be from either the patient
the vaccine will be used on or another patient. When they are from the patient
they will be used on, they are called autologous vaccines. These antigens
in these vaccines are more specific to the patient, but these vaccines are,
of course, more expensive to produce. Vaccines made from another patient
with the same type of tumor are called allogenic vaccines and are more cheaply
given to many people.
Cancer treatment with vaccines